what's up with Mirtazapine?

[doctordog]

I've tried most sleep aids without success. Benzos cause a paradoxical reaction. Seroquel gives me akathisia. Clonidine works at about 0.2mg but I feel very agitated and worked up the next day.

I've been using Doxylamine succinate -- up to 50mg -- over the past couple of weeks, occasionally switching in cyproheptadine as well. I notice tolerance builds quickly for some reason (maybe because I've been using them on and off for the past year). The past few days, 50mg of Doxylamine has done nothing .. I tried substituting it for 20mg of amitriptyline 4 hours before bed, but no response either.

Because I'm so desperate to sleep and it's such a huge ordeal every single night (long story), I asked my GP for Mirtazapine. My impression was it was *more* sedating at lower doses, so I took 7.5mg before bed. An hour later, I felt nothing except a little mental/physical sedation (cross-tolerance with anti-histamines?); anyway, for the hell of it, I thought I'd take the other 7.5mg and fell asleep within 5 minutes.

What happened? Was it more 5-HT antagonism at 15mg? Mirtazapine made my anxiety hell-ish when I tried it at 30mg a few years, and I feel a little on edge today (though kind of stoned as well), so I don't know how sustainable this can be.

But I'm wondering why 15mg knocked me out when 7.5mg didn't, and if I should maybe try an even lower dose, or possibly taking it earlier before bed?

 

[A2Z&NBETWEEN]

I don't know about them chemicals but for sleep for me..benzos work great idk Wut u mean by its paradoxical but as well I have had great luck with dream water , melatonin pills, liquor, Tylenol PM..that's bout it for me

 

[Lightning-Nl]

This question can be answered by common-sense really.

7.5MG's of Mirtazepine means that only 7.5MG's is going to enter the body. That means there will be less Mirtazepine available to antagonize H1, there will be less Mirtazepine to antagonize Adrenergic Receptors, and there will be less Mirtazepine to antagonize Serotoninergic receptors.

By taking 15MG's you increased the amount of available Mirtazepine. By increasing the amount of Mirtazepine in the body, you increased it's effects.

For some reason, people believe that Mirtazepine has stimulating properties all over the internet. It doesn't. This isn't a Dopamine/Norepinephrine reuptake inhibitor were talking about here, this is a Dopamine/Serotonin/Norepinephrine/Histamine/Acetylcholine antagonist. It has no stimulating properties. It's effects as a partial agonist at 5HT1a may provide mild stimulation, but the rest of the pharmacodynamic actions of Mirtazepine will overpower that easily.

In fact, Mirtazepine shouldn't even be considered an antidepressant. It's an antipsychotic.

 

[doctordog]

Well, it's not entirely common sense, because everything I've read indicates lower doses are more sedating. Maybe there was a balance struck between increased sedation and stimulation at 15mg that knocked me out.

However, you're incorrect re: stimulation properties. Of course, it's not a stimulant in the sense that it's abusable, but it is an alpha-2 antagonist, which promotes NE release. And it's not an anti-psychotic, because it isn't a selective dopamine antagonist. It's a tetracylic. TCA's antagonize similar receptors to Mirtazapine and aren't classified as 'antipsychotics'. At higher doses, Mirtazapine can induce mania in the vulnerable and would be more like to exacerbate psychosis than alleviate it.

 

[Lightning-Nl]

Well, it's not entirely common sense, because everything I've read indicates lower doses are more sedating. Maybe there was a balance struck between increased sedation and stimulation at 15mg that knocked me out.

There has never been a medical study to prove this to my knowledge. This has only ever been stated by users the of the drug. The only way this is correct is if you can turn up a medical study that proves your claim.

However, you're incorrect re: stimulation properties. Of course, it's not a stimulant in the sense that it's abusable, but it is an alpha-2 antagonist, which promotes NE release.

Only Alpha-2a antagonism would promote NE release and even if that's correct, it's effects are insignificant at best. Also, since Alpha-Adrenergic receptors are the main binding site of Norepinephrine, it wouldn't matter anyways. The Mirtazepine would block most, if not all stimulating effects caused by NE release. The only way NE could "over-power" Mirtazepines antagonistic effects on Alpha receptors is is it's NE effects were extremely significant (near the NE effect that Methylphenidate or Dextroamphetamine has - which Mirtazepine doesn't)

And it's not an anti-psychotic, because it isn't a selective dopamine antagonist.

What?

You have no idea what you're talking about. The word "selective" means that the substance in question has selectivity (a higher binding profile) for one receptor over another. What makes something an Antipsychotic is if it has no selectivity for the antagonization of dopaminergic receptors. By being selective to specific receptors, it's "less of" an antipsychotic.

Mirtazepine indeed is a "selective" dopamine antagonist because it's antagonistic effects on Dopamine are selective for D1, D2 and D3 Dopamine receptors.

It's a tetracylic.

Since you're getting technical with me, I'll get technical with you.

It's "technically" not a tetracyclic because medical literature classifies it as "Tricyclic Antidepressant." Does that mean it really does possess a tricyclic structure? No it doesn't. In fact, Mirtazepine is a "tetracyclic antidepressant" because of it's molecular structure. However, medical literature doesn't recognize it under that name.

At higher doses, Mirtazapine can induce mania in the vulnerable and would be more like to exacerbate psychosis than alleviate it.

"At higher doses" all antipsychotics produce psychotic effects. But were talking about doses 10X, 20X and 100X above the therapeutic range.

TCA's antagonize similar receptors to Mirtazapine and aren't classified as 'antipsychotics'.

TCA doesn't stand for "Tetracyclic antidepressant" it stands for "TRIcyclic antidepressant."

While Tricyclic Antidepressants have similar effects to Mirtazepine around the body, they do not have Dopaminergic effects (most of them anyways). Therefore, they cannot be classified as antipsychotics. Because Mirtazepines DOES have dopaminergic effects, it SHOULD be classified as an antipsychotic. It should also be classified as a "Tetracyclic Antidepressant." But it isn't.

You need to do a lot more research before you attempt to call someone out on something you're totally wrong about.

 

[BIGsherm7272]

Yea 7.5mg is a pretty low dose, the standard starting dose for sleep is 15mg, and most docs just write for 30mg right off the bat. Yes, like other anti-depressants that are mainly prescribed for sleep, such as trazodone, lower doses are better for sedation where higher doses are used to treat depression. But that doesn't mean the lowest possible strength works the best. For instance, 25mg of trazadone will do nothing for me, but 50-100mg will be effective for putting me to sleep. Same goes for mirtazapine. It's all about finding the right dosage for you.

I would stay on 15mg for as long as possible, so when your tolerance has risen you can move up to 30 and it will be effective again. I have been taking 15mg for almost 2 months and it is still working just fine for me. Mirtazapine tends to work a long time at the same dose. 30mg dosen't even really provide anymore sedation than 15mg does to me, it just hits me a little faster and harder. It has been the best sleep aid I have ever taken. I fall asleep blissfully and do no wake up feeling groggy, as can be the case with trazodone and seroquel (until you get use to them).

 

[doctordog]

Thanks BIGsherm. I have no interest in going up to 30mg, since, like I say, the anxiety was hell-ish, and I already feel a little overstimulated and dysphoric on 15mg. If it poops out, I'll probably just stop it.


Did you have any side-effects on 15mg along the lines of irritability or mood changes? Did they pass?

 

[dopemegently]

I started on 15 it wasn't enough to get me to sleep, so I upped my dose to 30 and bang! I take one, and 40 minutes later I'm so tired all I can do is sleep. Whatever antihistamine they put in those, they make dph look like sugar pills. Does anybody know what is in there? I'm hoping it's on the market and otc, because its the best non addicting sleep aid I've tried, bar none. Also there is zero abuse potential in whatever it is, unlike dph (when I was younger and had zero connects, I abused the hell out of those things, I'm talking stupidly high doses, bordering toxic)

 

[doctordog]

hmm, interesting .. I'm noticing some restless legs and akathisia now that the sedating effects are wearing off, so might give it one more night, otherwise I'm dumping it

 

[Flynnal]

I've always had irritability, talk to myself, get angry and nervous for no real reason, since I've been on Mirtazapine. But fucking hell if I can stop taking it? You've got to be kidding! I can't sleep a fucking wink without it. I'm on 15mg, but I WAS on 90mg taken 1 hour before bedtime and sure it knocked my ass out, but then I woke up 3-4 hours later, and had difficulty getting back to sleep, sometimes with racing thoughts.

The only good sleep aid for me, really, is Zolpidem. I don't like benzos or barbiturates for sleep, because you feel like you were hit in the head with a brick upon waking up. With Zolpidem I never had that effect, but I didn't feel that good either. But it was better than benzos or barbs.

Frankly I hate ALL sleep meds. Most don't work the way I want them to. Mirtazapine is probably the most benign but, like cannabis, also has it's own set of side effects and problems. If you can avoid mirtazapine and cannabis please, please do so. Once they poop out you're left hanging. It's NOT nice.

 

[doctordog]

Dang, so the irritability never passed? I can't live on 2 hours of sleep a night, which is basically what I get without any sleep aids .. I wish I could tolerate Zolpidem, I love the 15 minutes after I take it before I fall asleep (mild hallucinations, incredible sense of calm), but I get the worst rebound anxiety and suicidal ideation.

I might just use Mirtazapine as needed until I can see a psychiatrist again.

 

[dopemegently]

If I can't get a sleep aid I also become irritable. Well, not so much irritable as completely restless; I'll lay in bed ramrod straight, mind racing, and it's a miracle if I get to sleep at all without my mirt-guess it really shows how effective an antihistamine it is. I'm thinking of buying some doxylamine; are these any good?

 

[doctordog]

If you've been using Mirtazapine consistently, your antihistamine tolerance might be too high for Doxylamine to do anything. You might need to take a break for a couple of weeks.

Doxylamine is basically a last resort for me -- it works, but the sleep is crappy and I feel hungover the next day. It also makes me irritable.

 

[BIGsherm7272]

Thanks BIGsherm. I have no interest in going up to 30mg, since, like I say, the anxiety was hell-ish, and I already feel a little overstimulated and dysphoric on 15mg. If it poops out, I'll probably just stop it.


Did you have any side-effects on 15mg along the lines of irritability or mood changes? Did they pass?

Not at all. I usually have pretty low side-effects from most medications, at least compared to most other people. Within 30-45 minutes I get that stoned feeling, and pass out about 10-15 minutes after laaying down. I get awesome sleep on it and wake up feeling refreshed. But everyone reacts differently to medications.

If Remeron keeps causing you unwanted side-effects, you could always try something else. Doxepin was a very effective sleep aid for me, it is an old tricyclic anti-depressant. It made me pass out, and felt pretty good while doing so, but overslept everday (10-12 hours) and would wake up kinda groggy. Amytriptyline was also pretty effective, but not quite as effective as Remeron or Doxepin.

 

[bunge]

You should be able to experience an increase in sedation with mirtazapine upto the 60mgs+ mark and I wouldnt think you would get any stimulation until at least double that and even then I think an snri would have to be used as well.
Mirtazapine isnt better classed as an anti-psychotic as was suggested in this thread.
Its main action is as an inverse agonist and antagonist at serotonin and adrenergic receptors, its affinity for dopamine 1, 2 and 3 receptors is thousands of times less then its affinity for 5-ht and adrenergic receptors. Its like saying diphenhydramine is an anti-depressant because of its slight effect on sertonin!.
I think mirtazapine will end up having a wide range of uses in the future. Its already been shown to be useful as an ADJUNCT to anti-psych treatment because it can treat movement disorder side effects caused by the atypical meds and anecdotally as an acute treatment for serotonin syndrome.

 

[doctordog]

@bunge, Yeah, I was going to point that out, but couldn't be bothered arguing further -- the dopamine binding affinity is completely negligible.

I do find it stimulating, for some reason. My hands are a little shakey as I type this, I've had vasoconstriction all day, and I'm too scatterbrained to focus on anything for very long. It definitely isn't a placebo; I can usually tell something's up when my junk has shrunk to the size of an acorn (sorry, too-much-information). And it falls in line with my previous experience of 30mg being a nightmare. I've learned it takes 2 hours to hit peak plasma levels, so am maybe going to try a lower dose earlier in the night.

@ BIGsherm, amitriptyline in doses up to 30mg doesn't do anything for me .. tried Doxepin a few years ago and didn't have much success with it either.

 

[bunge]

I noticed some shakiness and aggression to next day for about 1-2 weeks but it passed eventually and thats when I really started to see the beneficial effects for my GAD and depression.
I think mirtazapine has a bright future as it works it wayout from under the shadow of the ssri's and various uses are being proposed for it, in addiction treatment, eating disorders and in combatting the side effects of other psych meds.
If you live outside the US then mianserin might be worth looking into. Its a sibling drug of mirtazapine in the tetra-cyclic class but is generally considered more potent then mirtazapine but is likely more toxic in overdose.

 

[dopemegently]

I'm surprised to hear some of the reactions people are having to it. I originally took citralopram, but it made me restless and I could barely sleep on it, so they changed me to mirtazipine. I might try asking my doctor about mianserin, as I'm becoming tolerant to the antihistamine in mirt. Btw is mirtazipine an SSRI?

 

[BIGsherm7272]

I'm surprised to hear some of the reactions people are having to it. I originally took citralopram, but it made me restless and I could barely sleep on it, so they changed me to mirtazipine. I might try asking my doctor about mianserin, as I'm becoming tolerant to the antihistamine in mirt. Btw is mirtazipine an SSRI?

No it is not, it is a Noradrenergic and specific Serotonergic Anti-Depressant (NaSSA).

 

[dopemegently]

I was on citralopram for 1 year; shouldn't I have had "SSRI discontinuation syndrome", by stopping it and taking mirt?